The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer

Heydari, Korosh; Saidijam, Massoud; Sharifi, Mohammadreza; Dermani, Fatemeh Karimi; Asl, Sara Soleimani; Shabab, Nooshin; Najafi, Rezvan

doi:10.1007/s12253-017-0222-6

Cited by 33 publications

(27 citation statements)

References 44 publications

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“…miR‐200c plays an important role in several biological processes such as EMT, apoptosis, cell invasion, metastasis, and drug resistance (Humphries & Yang, ). Our previous result showed that miR‐200c suppressed the EMT process and increased chemosensitivity of HCT‐116 cells (Heydari et al, ; Karimi Dermani et al, ).…”

Section: Discussionmentioning

confidence: 95%

Retracted: Zerumbone inhibits epithelial‐mesenchymal transition and cancer stem cells properties by inhibiting the β‐catenin pathway through miR‐200c

Dermani

Amini

Saidijam

et al. 2018

Journal Cellular Physiology

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Colorectal cancer (CRC) is one of the most lethal and rampant human malignancies in the world. Zerumbone, a sesquiterpene isolated from subtropical ginger, has been found to exhibit an antitumor effect in various cancer types. However, the effect of Zerumbone on the biological properties of CRC, including epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) has not been fully elucidated. Here, we investigated the inhibitory action of Zerumbone on the EMT process, CSC markers, and the β-catenin signaling pathway in the presence or absence of miR-200c. The effect of Zerumbone on HCT-116 and SW-48 cells viability was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of Zerumbone on EMT-related genes, CSCs markers, cell migration, invasion, sphere-forming, and β-catenin signaling pathway were explored. To evaluate the role of miR-200c in anticancer effects by Zerumbone, miR-200c was downregulated by LNA-anti-miR-200c. Zerumbone significantly inhibited cell viability, migration, invasion, and sphere-forming potential in HCT-116 and SW-48 cell lines. Zerumbone significantly suppressed the EMT and CSC properties as well as downregulated the β-catenin. Silencing of miR200c reduced the inhibitory effects of Zerumbone on EMT and CSCs in CRC cells. These data indicated that Zerumbone may be a promising candidate for reducing the risk of CRC progression by suppressing the β-catenin pathway via miR-200c.

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Section: Discussionmentioning

confidence: 95%

Retracted: Zerumbone inhibits epithelial‐mesenchymal transition and cancer stem cells properties by inhibiting the β‐catenin pathway through miR‐200c

Dermani

Amini

Saidijam

et al. 2018

Journal Cellular Physiology

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“…It has been revealed that the loss of miR‐200c expression contributes to the acquisition of EMT phenotype and drug resistance. Down‐regulation of miR‐200c by LNA technique has been shown to be associated with EMT phenotype while re‐expression of miR‐200c can result in the reversal of EMT phenotype …”

Section: Discussionmentioning

confidence: 99%

Retracted: miR‐200c, a tumor suppressor that modulate the expression of cancer stem cells markers and epithelial‐mesenchymal transition in colorectal cancer

Dermani

Amini

Saidijam

et al. 2018

J of Cellular Biochemistry

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Colorectal cancer (CRC) is the most frequently diagnosed cancer and the most common gastrointestinal cancer worldwide. Due to the presence of populations of cancer stem cells (CSCs) that cause recurrence, the possibility of cancer treatment is very low. The aim of current study was to evaluate the inhibitory role of miR-200c on EMT, CSCs markers and β-catenin in HCT-116 and SW48 cell lines. The expression of miR-200c, EMT-related genes, CSCs markers, and β-catenin were quantified by qRT-PCR. Further, expression of β-catenin and EMT-related proteins, and migration were analyzed by Western blot, and migration assay kit, respectively. Spheroid formation assay was used to enrich colorectal CSCs from colorectal cancer cell lines. LNA-anti-miR-200c suppressed the endogenous miR-200c in transfected cells compared with the control. qRT PCR and Western blot analysis of LNA-anti-miR-200c transfected cells revealed a considerable increase in CSCs markers, vimentin, ZEB-1, N-cadherin, and β-catenin expression, with a concomitant reduction in E-cadherin expression level. Migration and sphere forming ability of HCT-116 and SW48 cells increased in transfected cells. The results of current study revealed that downregulation of miR-200c may be an important factor for the overexpression of CSCs markers and EMT related genes via β-catenin upregulation in CRC.

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“…Hypoxia tumor microenvironment [37] and enhancement of autophagy procedure [38] both contribute to the chemoresistance of CRC cells. CRCs can also manipulate expression of multiple microRNAs to facilitate their chemoresistance, including suppressing expression of antitumor microRNAs, such as miR-181a/135a/302c [39], miR-874-3p [40], miR-200c [41]; and increasing tumorigenic miRNAs, such as miR-196b-5p [42], miR-315b [43], miR-10b [44].…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Doublecotin-like kinase 1 increases chemoresistance of colorectal cancer cells through the anti-apoptosis pathway

Jones

Mei

2019

Preprint

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Colorectal cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer-related deaths in the United States. About 50% of CRC patients relapsed after surgical resection and ultimately died of metastatic disease. Cancer stem cells (CSCs) are believed to be the primary reason for the recurrence of CRC. Specific stem cell marker, doublecortin-like kinase 1 (DCLK1) plays critical roles in initiating tumorigenesis, facilitating tumor progression, and promoting metastasis of CRC. It is up-regulated in CRC and upregulation of DCLK1 indicates poor prognosis. Whether DCLK1 is correlated with enhanced chemoresistance of CRC cells is unclear. Our research aims to reveal association of DCLK1 with chemoresistance of CRC cells and the underlying molecular mechanisms. In order to achieve our goal, we established stable DCLK1 over-expression cells (DCLK1+) using the HCT116 cells (WT). DCLK1+ and WT cells were treated with 5-Fluorouracil (5-Fu) at different doses for 24 or 48 hours. MTT assay was used to evaluate cell viability and IC 50 of 5-Fu was determined. Quantitative real time PCR was applied to determine gene expression of caspase-3 (casp-3), caspase-4 (casp-4), and caspase-10 (casp-10). Cleaved casp-3 expression was investigated using Western blot and immunofluorescence. Our results demonstrated that IC 50 of 5-Fu for the DCLK1+ cells was significantly higher than that of the WT cells for both 24 and 48hour treatment (P=0.002 and 0.048 respectively), indicating increased chemoresistance of the DCLK1+ cells. Gene expression of casp-3, casp-4, and casp-10 were significantly inhibited in the DCLK1+ cells after 5-Fu treatment compared to the WT cells (P=7.616e-08, 1.575e-05 and 5.307e-08, respectively). Cleaved casp-3 amount and casp-3 positive cells were significantly decreased in the DCLK1+ cells after 5-Fu treatment compared to the WT cells (P=0.015). In conclusion, our results demonstrated that DCLK1 overexpression enhanced the chemoresistance of CRC cells to 5-Fu treatment by suppressing gene expression of key caspases in the apoptosis pathway and activation of apoptosis pathway. DCLK1 can be an intriguing therapeutic target for the effective treatment of CRC patients.

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The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer

Cited by 33 publications

References 44 publications

Retracted: Zerumbone inhibits epithelial‐mesenchymal transition and cancer stem cells properties by inhibiting the β‐catenin pathway through miR‐200c

Retracted: Zerumbone inhibits epithelial‐mesenchymal transition and cancer stem cells properties by inhibiting the β‐catenin pathway through miR‐200c

Retracted: miR‐200c, a tumor suppressor that modulate the expression of cancer stem cells markers and epithelial‐mesenchymal transition in colorectal cancer

Doublecotin-like kinase 1 increases chemoresistance of colorectal cancer cells through the anti-apoptosis pathway

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